Methods of treatment using sustained release sotalol formulations

Abstract

Sustained release compositions of sotalol, or a pharmaceutically acceptable salt thereof, are provided. In certain examples, sotalol, or a pharmaceutically acceptable salt thereof, may be administered in an effective amount to provide a therapeutic effect to a patient, such as, for example, a patient suffering from a cardiac disorder. In some examples, sotalol combined with a sustained release system may be administered to provide a sustained release of sotalol for a desired period, e.g., at least about 24 hours.

What is claimed is: 
     
       1. A method of preparing a sustained release composition comprising:
 preparing a sustained release composition comprising:
 an effective amount of a racemic mixture of D-sotalol and L-sotalol, or 
 a pharmaceutically acceptable salt thereof; and 
 a sustained release system, whereby the sustained release system is at least one of a topical, rectal, oral and parenteral system, and is effective to provide sustained release of the racemic mixture of D-sotalol and L-sotalol or the pharmaceutically acceptable salt thereof for at least about 24 hours when exposed to an environmental fluid, and wherein such sustained release composition provides reduced beta-blockade relative to non-racemic sotalol, and lengthened cardiac repolarization, 
 
 combining the sustained release composition with a gum to provide a drug/gum ratio determined to provide a desired degree of sustained release; and 
 tableting the combined sustained release composition and the gum to form a tablet. 
 
     
     
       2. The method of  claim 1 , wherein the sustained release system is at least one of a rectal and oral system. 
     
     
       3. The method of  claim 1 , wherein the 24 hours is any other period that is a sustained period relative to conventional drug activity. 
     
     
       4. The method of  claim 1 , wherein the racemic mixture of D-sotalol and L-sotalol or pharmaceutically acceptable salt thereof is the sole active ingredient of the sustained release composition. 
     
     
       5. The method of  claim 1 , wherein the gum comprises a homopolysaccharide gum. 
     
     
       6. The method of  claim 1 , wherein the gum comprises a heteropolysaccharide gum. 
     
     
       7. The method of  claim 1 , wherein the gum comprises a homopolysaccharide gum and a heteropolysaccharide gum. 
     
     
       8. The method of  claim 1 , wherein the gum is capable of cross-linking; wherein the tablet further comprises an inert pharmaceutical diluent; and a pharmaceutically acceptable cationic cross-linking agent capable of cross-linking with the gums and increasing the gel-strength of the gums. 
     
     
       9. A method of preparing a sustained release composition comprising:
 preparing a sustained release composition comprising:
 an effective amount of a racemic mixture of D-sotalol and L-sotalol, or 
 a pharmaceutically acceptable salt thereof; and 
 a sustained release system, whereby the sustained release system is at least one of a topical, rectal, oral and parenteral system, and is effective to provide sustained release of the racemic mixture of D-sotalol and L-sotalol or the pharmaceutically acceptable salt thereof for at least about 24 hours when exposed to an environmental fluid, and wherein such sustained release composition is for use in the treatment of arrhythmia with reduced beta-blockade and for lengthening cardiac repolarization, and 
 
 quantifying the sustained release composition into discrete unit forms such that each unit includes a dose of sotalol in an effective amount to provide a therapeutic effect for at least about 24 hours. 
 
     
     
       10. The method of  claim 9 , wherein the gum comprises a homopolysaccharide gum. 
     
     
       11. The method of  claim 9 , wherein the gum comprises a heteropolysaccharide gum. 
     
     
       12. The method of  claim 9 , wherein the gum comprises a homopolysaccharide gum and a heteropolysaccharide gum. 
     
     
       13. The method of  claim 9 , wherein the gum is capable of cross-linking; wherein the tablet further comprises an inert pharmaceutical diluent; and a pharmaceutically acceptable cationic cross-linking agent capable of cross-linking with the gums and increasing the gel-strength of the gums. 
     
     
       14. A method of preparing a sustained release composition comprising:
 preparing a sustained release composition comprising:
 a racemic mixture of D-sotalol and L-sotalol or a pharmaceutically acceptable salt thereof, wherein the sustained release is maintained for at least 24 hours, wherein a therapeutically effective amount provides reduced beta-blockade relative to a composition that does not include a racemic mixture of D-sotalol and L-sotalol, and lengthened cardiac repolarization, 
 wherein the racemic mixture of D-sotalol and L-sotalol or pharmaceutically acceptable salt thereof is the sole active ingredient of the sustained release composition, and 
 
 quantifying the sustained release composition into discrete unit forms such that each unit includes a dose of sotalol in an effective amount to provide a therapeutic effect for at least about 24 hours. 
 
     
     
       15. The method of  claim 14 , wherein the gum comprises a homopolysaccharide gum. 
     
     
       16. The method of  claim 14 , wherein the gum comprises a heteropolysaccharide gum. 
     
     
       17. The method of  claim 14 , wherein the gum comprises a homopolysaccharide gum and a heteropolysaccharide gum. 
     
     
       18. The method of  claim 14 , wherein the gum is capable of cross-linking; wherein the tablet further comprises an inert pharmaceutical diluent; and a pharmaceutically acceptable cationic cross-linking agent capable of cross-linking with the gums and increasing the gel-strength of the gums.